How Crystal Specifications Influence Pharmaceutical Tablets?

Paracetamol (acetaminophen) is an active pharmaceutical ingredient (API) known for its poor tabletability, mainly because of low flow- and compression-abilities. Several approaches have been proposed to improve this, including modifying crystal shape and size, changing the maximum punch compaction pressure during tablet making, and utilizing formulations with higher percentage of excipient.

In this work, we are using the first approach by investigating the influence of crystal shape and size. To do that, we use three different crystals of paracetamol with different habit and sizes and will characterize the resulting tablets (pure as well as complete formulations) manufactured using direct compression both as single tablets and in continuous fashion.

For pure paracetamol tablets, we have observed that the tensile strength and compaction profile are strongly size and shape dependent. For formulation tablets, tensile strength, friability, dissolution and disintegration profiles are being investigated. We hypothesize that the crystal habit (shape) is the influencing factor in such settings. The present study provides a comprehensive data set that enables the prediction of the relation between crystal specification, direct compression setting, and quality of the final products.